A Phase 3 trial of BCG with or without pembrolizumab for high risk non-muscle invasive bladder cancer (KEYNOTE-676)
- Conditions
- High-risk Non-muscle Invasive Bladder Cancer (NMIBC)MedDRA version: 21.1Level: LLTClassification code 10022877Term: Invasive bladder cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001967-22-GB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 550
1. Male/female participants who are at least 18 years of age on the day of signing informed consent will be enrolled in this study
2. Have histologically confirmed by BICR diagnosis of high-risk non-muscle invasive (T1, highgrade Ta and/or CIS) TCC of the bladder
3. Have been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC defined as at least 5 intravesical instillations of BCG within a 10 week period of time. If more than one induction course or any maintenance therapy of BCG has been received, the participant is not eligible for this study
4. Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC defined as:
a. HR NMIBC: recurrent T1, high-grade Ta and/or CIS
b. Persistent: remains present within 3 months (-2 weeks) to 6 months (+4 weeks) after start of BCG induction, or
c. Recurrent: reappearance of high-risk NMIBC after achieving a CR or tumorfree state within 6 months (+ 4 weeks) after start of BCG induction. The recurrence must be within 24 months of last exposure to BCG (with up to an additional 56 days allowed to account for delays in the 24 month assessment)
5. Have undergone cystoscopy/TURBT to remove all resectable disease within 12 weeks prior to randomization. Participants with recurrent T1 disease should have undergone a restaging TURBT procedure between 14 to 56 days prior to randomization to confirm complete resection and that the participant continues to meet eligibility criteria.
-If restaging TURBT is performed between 14 to 56 days prior to randomization and the absence of muscle invasive tumor (=T2) is confirmed by central pathology review, participants are still eligible even if first TURBT was performed >12 weeks prior to randomization.
- Tissue resected during restaging TURBT must be sent to central pathology lab for tumor histology evaluation with results confirming eligibility prior to randomization.
6. Have provided tissue for biomarker analysis from the most recent TURBT/biopsy procedures from which tumor sample is available. The PD-L1 status of the archived or recently-obtained biopsy specimen must be determined by the central laboratory prior to randomization. If submitting unstained cut slides, freshly cut slides should be submitted
7. Have a performance status of 0, 1 or 2 on the ECOG Performance Scale, as assessed within 14 days prior to randomization
8. Have adequate organ function. Specimens must be collected within 14 days prior to randomization
9. A male participant must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
10. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a) Not a WOCBP
OR
b) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment
11. The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the study. The participant may also provide consent/assent for future biomedical research. However the participant may participate in the main study without participating in future biomedical research
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 138
F.1.3 Elde
1. Has persistent (remains present or occurs within 3 months (-2 weeks) to 6 months (+4 weeks) after start of BCG induction) T1 disease following an induction course of BCG
2. Has a history or concurrent muscle invasive (ie, T2, T3, T4), locally advanced non-resectable or metastatic UC.
3. Has concurrent extra-vesical (ie, urethra, ureter, renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium, concurrent upper tract involvement, or invasive prostatic TCC including T1 or greater disease, or ductal invasion
4. A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
6. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks of start of study treatment
7. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
8. Has received a live vaccine within 30 days of start of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, bacillus Calmette Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed
9. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of start of study treatment
10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days of start of study treatment
11. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
12. Has hypersensitivity to pembrolizumab and/or any of its excipients
13. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
14. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
15. Has one or more of the following contraindications to BCG: prior BCG sepsis or systemic infection, total bladder incontinence, or an adverse experience to a previous BCG instillation that resulted in treatment discontinuation and precludes retreating with BCG
16. Has an active infection requiring systemic therapy (including a symptomatic UTI)
17. Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority
18. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. No testing for Hepatitis B and Hepatitis C is required unles
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method